Phenyl-3-pyridinylmethanone → Phenyl(3-phenyl-2,4-bis(trifluoromethyl)quinolin-6-yl)(pyridin-3-yl)methanol

Participants

Reaction Steps

A ˜−70° C. solution of 6-bromo-3-phenyl-2,4-bis(trifluoromethyl)quinoline (66.8 mg, 0.159 mmol, Intermediate 8, step c) in THF (0.9 mL) was treated dropwise with n-BuLi (0.12 mL, 1.59 M, 0.191 mmol) via syringe under argon over 1 min. After stirring for less than 1 min, the dark homogeneous solution was treated with a solution of phenyl(pyridin-3-yl)methanone (32.0 mg, 0.175 mmol, Aldrich) in THF (0.6 mL) over 2 min, and the resulting dark amber solution was stirred at ˜−70° C. while the cold bath was allowed to expire over 4 hours. The amber solution was then partitioned with 5 M NH4Cl (2 mL) and EtOAc (5 mL), and the organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by C18 HPLC (20% to 100% CH3CN, with 0.1% TFA throughout) to provide, after lyophilization, the title compound as a white solid. 1H NMR (400 MHz, MeOH-d4) δ 8.87 (s, 1H), 8.78 (d, J=5.38 Hz, 1H), 8.47 (d, J=8.07 Hz, 1H), 8.27-8.39 (m, 2H), 7.92-8.05 (m, 2H), 7.26-7.54 (m, 10H); MS m/e 568.0 [M+H]+.

Provenance & Evidence